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Identification of linear viscoelastic constitutive models.

Accelerations induce in the brain mechanical stresses that may explain the loss of consciousness feared by fighter pilots. In this study, the brain is modelled as a multi-domain structure and a finite element method is used to identify the constitutive law parameters of each domain and then to analyse the stress level in the brain. The loading and observed strain rates induced by hypergravity seem to indicate a quasi-static behaviour of the brain structure. A general procedure has been developed to characterise the behaviour of a structure including several domains. Each of them is assumed to be isotropic and homogeneous with a linear viscoelastic behaviour. These constitutive laws were identified using only the displacements of several nodes on the envelope discarding the displacements between domains at the interaction surfaces. These interfaces may be buried inside the structure and not connected with the external surface. Two validation examples are proposed to show the reliability and effectiveness of the method.

Acceleration↗

Sexual dimorphism in cerebellar structure, function, and response to environmental perturbations.

Sexual dimorphism of CNS structure and function has been observed in humans and animals, but remains relatively unrecognized in the context of the cerebellum. Recent research in our laboratory has examined whether these gender differences extend to cerebellar structure and function, as well as the impact of environmental factors on the developing cerebellum. Perinatal exposure to both chemical and physical perturbations in the environment (in our experiments, PCBs or hypergravity) affects growth, neurodevelopment, and motor coordination differently in males and females. These neurodevelopmental and behavioral effects are accompanied by sex-related changes in cerebellar mass and cerebellar protein expression. Exposure to chemical toxins (PCBs) resulted in more dramatic neurodevelopmental and behavioral changes in male neonates. It is possible that gender-related differences in male and female cerebellar structure and function are related to sex-specific development of the cerebellum and sex-specific distribution of specific receptors, local synthesis of trophic factors, and maturation of the pituitary hypophesial axis. These sex-related differences may underlie the sex-specific preponderance of certain neuropsychiatric disorders, and must be incorporated in the design of future basic and clinical investigations.

Animals↗

Crickets in space.

"Crickets in Space" (CRISP) was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal activation systems. These advantages allowed us to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to microgravity and hypergravity (hg) while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3g-conditions concerning their soma sizes but not their topographical arrangement. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity. The contrary physiological and behavioral results indicate a facilitation of 1g-readaptation by accessory gravity. proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of microgravity or hg-exposure related to the period of neuronal proliferation. Grant numbers: 50WB9553-7.

Adaptation, Physiological↗

On the influence of altered gravity on the growth of fish inner ear otoliths.

Inner ear stones (otoliths) of developing cichlid fish (Oreochromis mossambicus) were marked with the calcium tracer alizarin-complexone (AC) at 1g-earth gravity before and after a longterm (20 days) stay of the animals at moderate hypergravity conditions (3g; centrifuge). AC deposition at the otoliths resulted in two fluorescence bands, which enclosed the area grown during exposure to altered gravity. This area was measured with regard to size and asymmetry (size difference between the left and the right stones). Both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure as compared to parallely raised 1 g-control specimens. The asymmetry concerning the lapilli was pronouncedly decreased in comparison to the 1g-controls. These findings suggest, that the growth and the development of bilateral asymmetry of otoliths is guided by the environmental gravity vector. Some of the hyper-g animals revealed a kinetotic behaviour at the transfer from hyper-g to normal 1g-earth gravity conditions, which was qualitatively similar to the behaviour observed in previous experiments at the transfer from 1 g to microgravity in the course of parabolic aircraft flights. The lapillar asymmetry of kinetotic samples was found to be significantly higher than that of normally behaving experimental specimens. This result supports an earlier theoretical concept, according to which human static space sickness might be based on asymmetric utricular otoliths

Animals↗

Behavioural changes induced by early and long-term gravito-inertial force modification in the rat.

The study concerns rats conceived, born and raised in a hypergravity environment (HG: 2 g) for 3 months using a centrifuge. They were then exposed to terrestrial gravity (1 g) and submitted to behavioural tests investigating their spontaneous locomotor activity (open-field), their posture (support surface), and their vestibular function (air-righting reflex). Performances were compared to age-matched control rats housed at 1 g for the same time period. Results showed static and dynamic behavioural deficits as early as the rats were exposed to normal gravity. They exhibited strongly increased motor activity in open-field, with longer travelled distances and more scattered trajectories; in addition, the HG rats displayed more numerous rearings than controls did. They showed postural changes characterized by an enlarged support surface and they did not succeed in the air-righting reflex, due to increased time-delay for head righting. None of these changes were permanent. Indeed, for all tests, the HG rats tested after 3 weeks spent in normal terrestrial gravity exhibited behaviours similar to those of the controls. HG-induced changes in the functional properties of the vestibular system may explain the deficits showed by the HG rats once exposed to normal gravity. The adaptation process to 1 g leading to the appearance of normal behaviour takes about 3 weeks. It likely implicates a central re-evaluation of the sensory inputs and an updating of the motor commands.

Adaptation, Physiological↗

Graviorientation in protists and plants.

Gravitaxis, gravikinesis, and gravitropism are different graviresponses found in protists and plants. The phenomena have been intensively studied under variable stimulations ranging from microgravity to hypergravity. A huge amount of information is now available, e.g. about the time course of these events, their adaptation capacity, thresholds, and interaction between gravity and other environmental stimuli. There is growing evidence that a pure physical mechanism can be excluded for orientation of protists in the gravity field. Similarly, a physiological signal transduction chain has been postulated in plants. Current investigations focus on the question whether gravity is perceived by intracellular gravireceptors (e.g. the Muller organelle of the ciliate Loxodes, barium sulfate vacuoles in Chara rhizoids or starch statoliths in higher plants) or whether the whole cell acts as a sedimenting body exerting pressure on the lower membrane. Behavioral studies in density adjusted media, effects of inhibitors of mechano-sensitive ion channels or manipulations of the proposed gravireceptor structures revealed that both mechanisms have been developed in protists and plants. The threshold values for graviresponses indicate that even 10% of the normal gravitational field can be detected, which demands a focusing and amplifying system such as the cytoskeleton and second messengers.

Animals↗

Features of vestibuloocular reflex modulations induced by altered gravitational forces in tadpoles (Xenopus laevis).

In Xenopus laevis tadpoles, we studied the static vestibuloocular reflex (rVOR) in relation to modifications of the gravitational environment to find basic mechanisms of how altered gravitational forces (AGF) affect this reflex. Animals were exposed to microgravity during space flight or hypergravity (3g) for 4 to 12 days. Basic observations were that (1)the development of the rVOR is significantly affected by altered gravitational conditions, (2) the duration of 1g-readaptation depends on the strength of the test stimulus, (3) microgravity induces malformations of the body which are related to the rVOR depression. Future studies are based on the hypotheses (1) that the vestibular nuclei play a key roll in the adaptation to AGF conditions, (2) that the stimulus transducing systems in the sense organ are affected by AGF conditions, and (3) that fertilized eggs will be converted to normal adults guided by physiological and morphological set points representing the genetic programs. Developmental retardation or acceleration, or otherwise occurring deviations from standard development during embryonic and postembryonic life will activate genes that direct the developmental processes towards normality.

Adaptation, Physiological↗

Gravity related research with fishes--perspectives in regard to the upcoming International Space Station, ISS.

During the entire evolution of life on Earth, the development of all organisms took place under constant gravity conditions, against which they achieved specific countermeasures for compensation and adaptation. On this background, it is still an open question to which extent altered gravity such as hypergravity (centrifuge) or microgravity (spaceflight) affects the normal individual development, either on the systemic level of the whole organism or on the level of individual organs or even single cells. The present review provides information on these questions, comprising gravistimulated effects on invertebrates and vertebrates (with the exception of mammals, since respective biomedically oriented reviews abound), focusing on developing fish as model systems, with special emphasis on the effect of altered gravity on the developing brain and vestibular system, comprising investigations on behaviour and plastic reactivities of the brain and inner ear. Clues and insights into the possible basic causes of space motion sickness-phenomena (SMS; a kinetosis) are provided as well as perspectives in regard to future work to be done including studies on the ISS concerning the analysis of gravistimulated effects on developmental issues (imprinting phase for graviperception?).

Adaptation, Physiological↗

Bone metabolism and formation of mice bred in a 2 G environment.

The purpose of this study is to reveal the effect of chronic hypergravity exposure on the bone formation and the bone metabolism when mammals produce offspring in a 2 G environment. We measured the length and width of the thighbone, the length of the pelvis, the width of the pelvic cavity and the width of the fourth cervical vertebra on the second (F2) and the third (F3) generation mice bred in a 2 G environment every ten days from 20 days old to 60 days old in an experiment on bone formation. In an experiment on bone metabolism, we measured calcium and phosphorus in the bones of the F3 in the 2 G group. Ratios of the thighbone length, pelvis length, pelvic cavity width, and fourth cervical vertebra width versus the body length were calculated. These ratios were higher in the 2 G group than the control group during all measuring periods. Calcium and phosphorus concentrations in the thighbone and the lumbar vertebra were lower in the 2 G group than in the control group. However, the calcium and phosphorus concentrations in the cervical vertebrae of the 2 G group were higher. These results suggest that the influence of gravity load may vary in the bones.

Animals↗

Studies toward birth and early mammalian development in space.

Sustaining life beyond Earth on either space stations or other planets will require a clear understanding of how the space environment affects key phases of mammalian reproduction and development. Pregnancy, parturition (birth) and the early development of offspring are complex processes essential for successful reproduction and the proliferation of mammalian species. While no mammal has yet undergone birth within the space environment, studies spanning the gravity continuum from 0- to 2-g are revealing startling insights into how reproduction and development may proceed under gravitational conditions deviating from those typically experienced on Earth. In this report, I review studies of pregnant Norway rats and their offspring flown in microgravity onboard the NASA Space Shuttle throughout the period corresponding to mid- to late gestation, and analogous studies of pregnant rats exposed to hypergravity (hg) onboard the NASA Ames Research Center 24-ft centrifuge. Studies of postnatal rats flown in space or exposed to centrifugation are reviewed. Although many important questions remain unanswered, the available data suggest that numerous aspects of pregnancy, birth and early mammalian development can proceed under altered gravity conditions.

Animals↗

The identification of gravikinesis from ciliates: methods and experience.

Recent advances in the gravitational physiology of ciliates are reported: the theoretical and experimental assessment of gravikinesis and sedimentation, calculation of gravikinesis using slopes of observed swimming and sedimentation data under hypergravity, orientational distributions of gravikinesis, central and membrane-associated gravitransduction, and the kinetics of activation and relaxation of gravikinesis.

Animals↗

Fish otolith growth in 1g and 3g depends on the gravity vector.

Size and asymmetry (size difference between the left and the right side) as well as calcium (Ca) content of inner ear otoliths of larval cichlid fish Oreochromis mossambicus were determined after a long-term stay at hypergravity conditions (3g; centrifuge). Both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure as compared to parallely raised 1g-control specimens and the absolute amount of otolith-Ca was diminished. The asymmetry of sagittae was significantly increased in the experimental animals, whereas the respective asymmetry concerning lapilli was markedly decreased. In the course of another experiment larvae were raised in aquarium hatch baskets, from which one was placed directly above aeration equipment which resulted in random water circulation shifting the fish around ("shifted" specimens). The lapillar asymmetry of the "stationary" specimens showed a highly significant increase during early development when larvae were forced to lay on their sides due to their prominent yolk-sacs. In later developmental stages, when they began to swim freely, a dramatic decrease in lapillar asymmetry was apparent. Taken together with own previous findings according to which otolith growth stops after vestibular nerve transaction, the results presented here suggest that the growth and the development of bilateral asymmetry of otoliths is guided by the environmental gravity vector, obviously involving a feedback loop between the brain and the inner ear.

Animals↗

Susceptibility to abnormal (kinetotic) swimming fish correlates with inner ear carbonic anhydrase-reactivity.

Larval cichlid fish (Oreochromis mossambicus) were kept at hypergravity (hg; centrifuge) for 6 h. Following the transfer to 1 g (i.e. stopping the centrifuge), animals were separated into normally and abnormally (kinetotic) swimming individuals (the latter were swimming kinetotically, i.e. performing spinning movements). Subsequently, carbonic anhydrase- (CA-) reactivity was histochemically demonstrated and densitometrically determined in inner ear maculae. It was found that both the total macular CA-reactivity as well as the difference in reactivates between left and right maculae were significantly lower in normally swimming hg-animals as compared to the kinetotically behaving hg-fish (P<0.0001). This result is in complete agreement with closely related studies carried out on the calcium incorporation of inner ear otoliths and indicates that a regulatory mechanism, which adjusts otolithic calcium carbonate incorporation towards the gravity vector, acts via activation/deactivation of macular CA.

Acoustic Maculae↗

Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity-changing stress: involvement of E-64-sensitive proteases in suppression of UV mutagenicity.

Under the 1G condition, the increase in antipain-sensitive protease activity promptly after UV (mainly 254 nm wavelength) irradiation in cultured human cells is detected and found to be one of the intriguing events involved in suppression of cell mutability. It was found that two cell lines, RSa and its variant UVAP-1 cells are applicable; the former is hypermutable and not susceptible to protease activation, while the latter is hypomutable and susceptible. In the present study it was investigated whether the increase in protease activity by UV irradiation is also observed in hypomutable human UVAP-1 cells exposed to gravity-changing stress and whether the increase is involved in suppression of UV mutagenicity. Exposure of human UVAP-1 cells to gravity-changing stress such as free-fall and parabolic flight prior to UV irradiation resulted in a pronounced increase in protease activity, but not to hypergravity conditions (2 and 10G) prior to UV irradiation. To characterize the proteases, components of lysates from the cells exposed to free-fall prior to UV irradiation were fractionated by high performance liquid chromatography, indicating two separate fractions with highly increased levels of E-64-sensitive protease activity. In the cells treated with E-64 during their exposure to free-fall, K-ras codon 12 base substitution mutation was detected after UV irradiation, although the mutation was not detected after UV irradiation alone. Thus, the increase in E-64-sensitive protease activity may be involved in the suppression of UV mutagenicity in UVAP-1 cells exposed to free-fall.

Antipain↗

Focused Assessment with Sonography for Trauma in weightlessness: a feasibility study.

BACKGROUND: The Focused Assessment with Sonography for Trauma (FAST) examines for fluid in gravitationally dependent regions. There is no prior experience with this technique in weightlessness, such as on the International Space Station, where sonography is currently the only diagnostic imaging tool. STUDY DESIGN: A ground-based (1 g) porcine model for sonography was developed. We examined both the feasibility and the comparative performance of the FAST examination in parabolic flight. Sonographic detection and fluid behavior were evaluated in four animals during alternating weightlessness (0 g) and hypergravity (1.8 g) periods. During flight, boluses of fluid were incrementally introduced into the peritoneal cavity. Standardized sonographic windows were recorded. Postflight, the video recordings were divided into 169 20-second segments for subsequent interpretation by 12 blinded ultrasonography experts. Reviewers first decided whether a video segment was of sufficient diagnostic quality to analyze (determinate). Determinate segments were then analyzed as containing or not containing fluid. A probit regression model compared the probability of a positive fluid diagnosis to actual fluid levels (0 to 500 mL) under both 0-g and 1.8-g conditions. RESULTS: The in-flight sonographers found real-time scanning and interpretation technically similar to that of terrestrial conditions, as long as restraint was maintained. On blinded review, 80% of the recorded ultrasound segments were considered determinate. The best sensitivity for diagnosis in 0 g was found to be from the subhepatic space, with probability of a positive fluid diagnosis ranging from 9% (no fluid) to 51% (500 mL fluid). CONCLUSIONS: The FAST examination is technically feasible in weightlessness, and merits operational consideration for clinical contingencies in space.

Aerospace Medicine↗

Lower body negative pressure treadmill exercise is more comfortable and produces similar physiological responses as weighted vest exercise.

Lower body negative pressure (LBNP) treadmill exercise can generate a hypergravity load on the lower body that may improve athlete performance by mechanical and cardiovascular adaptations. This study compared the cardiovascular responses, subjective exertion and discomfort levels produced by LBNP exercise with those generated by a weighted vest (WV). We hypothesized that LBNP exercise is more comfortable than WV exercise at comparable levels of exercise. Nine subjects exercised on a treadmill at nine conditions, at 5.5 mph for 15 minutes, in which they ran in random order to avoid confounding effects: 100 %, 110 %, 120 %, 130 %, and 140 % body weight (BW), the latter four conditions were achieved by either LBNP chamber or WV. Heart rate (HR) and oxygen consumption (.VO(2)) were monitored continuously using ECG and open circuit spirometry. At the end of each test, subjects were asked to give discomfort and exertion scores using a ten-point visual analog scale (10 = maximal discomfort and exertion). For both HR and .VO(2), no significant differences were observed between LBNP and WV. Subjects reported significantly higher discomfort levels when exercising with the WV than with the LBNP at 120 % BW (5.1 +/- 0.55 vs. 3.1 +/- 0.64; p < 0.05), 130 % BW (6.2 +/- 0.42 vs. 2.3 +/- 0.44; p < 0.01) and 140 % BW (6.9 +/- 0.27 vs. 4.7 +/- 0.60; p < 0.01), while maintaining similar exertions at all conditions. Based on these results, LBNP exercise is more comfortable than standard WV exercise, while maintaining similar exertion, HR and .VO(2) values.

Adult↗

Fertilization of sea urchin eggs and sperm motility are negatively impacted under low hypergravitational forces significant to space flight.

Sperm and other flagellates swim faster in microgravity (microG) than in 1 G, raising the question of whether fertilization is altered under conditions of space travel. Such alterations have implications for reproduction of plant and animal food and for long-term space habitation by man. We previously demonstrated that microG accelerates protein phosphorylation during initiation of sperm motility but delays the sperm response to the egg chemotactic factor, speract. Thus sperm are sensitive to changes in gravitational force. New experiments using the NiZeMi centrifugal microscope examined whether low hypergravity (hyperG) causes effects opposite to microG on sperm motility, signal transduction, and fertilization. Sperm % motility and straight-line velocity were significantly inhibited by as little as 1.3 G. The phosphorylation states of FP130, an axonemal phosphoprotein, and FP160, a cAMP-dependent salt-extractable flagellar protein, both coupled to motility activation, showed a more rapid decline in hyperG. Most critically, hyperG caused an approximately 50% reduction in both the rate of sperm-egg binding and fertilization. The similar extent of inhibition of both fertilization parameters in hyperG suggests that the primary effect is on sperm rather than eggs. These results not only support our earlier microG data demonstrating that sperm are sensitive to small changes in gravitational forces but more importantly now show that this sensitivity affects the ability of sperm to fertilize eggs. Thus, more detailed studies on the impact of space flight on development should include studies of sperm function and fertilization.

Animals↗

Hyper- and hypogravity alter posture in rats compensated on Earth for a vestibular asymmetry.

Head posture and neck muscle activity (EMGs) were examined in unilateral (UL) and bilateral (BL) vestibularly lesioned rats in hypergravity (1.7 g) and hypogravity (0 g) during parabolic flights. Compared with BL rats taken as control, the head and the body of UL deviated toward the lesion side at 0 g and toward the intact side at 1.7 g. Recorded in head fixed condition, left and right EMGs remained symmetrical in BL while UL rats displayed an asymmetry between left and right muscles at 1.7 g, but not at 0 g. These results demonstrate that an experimental otolithic asymmetry, compensated on Earth, can become unbalanced in altered gravity. Paradoxically, the utricular system appears to play a major role in that process.

Animals↗